Using biotinylated self antigens (e.g., thyroglobulin insulin, etc.) and fluoresceine activated cell sorter human B lymphocytes that bind to these antigens have been selected. These cells have been immortalized using Epstein-Barr virus into monoclonal antibody producing cell lines. These cell lines have been stabilized by fusing them with human myeloma cells. To determine the potential human B cell repertoire against self antigens by limiting dilution analysis we have determined the frequencies of B cells producing IgM, IgG and IgA antibodies to thyroglobulin, insulin, ssDNA and the Fc fragments of IgG. Monoclonal anti-idiotypic (anti-Id) antibodies have been made against some of the human monoclonal autoantibodies. One of these anti-ids when inoculated into rabbits induced an anti-anti-Id antibody. These anti-anti-Ids showed specificities similar to that of the original human monoclonal autoantibody and suggested that an anti-Id can trigger a cascade of autoimmune responses. Peripheral blood lymphocytes obtained from both normals and patients with autoimmune disorders when cultured give raise to spontaneously proliferating lymphocytes that produce autoantibodies. Epstein-Barr virus antigens are found in these cells and are thought to be responsible for the transformation. These studies very strongly suggest that the EBV infected B cells may be responsible for the autoantibodies found in patients who are on immunosuppressive therapy, with AIDS and other diseases in which the immune system is perturbed.